Update of Endocrine Dysfunction following Pediatric Traumatic Brain Injury

Abstract

Traumatic brain injuries (TBI) are common occurrences in childhood, often resulting in long term, life altering consequences. Research into endocrine sequelae following injury has gained attention; however, there are few studies in children. This paper reviews the pathophysiology and current literature documenting risk for endocrine dysfunction in children suffering from TBI. Primary injury following TBI often results in disruption of the hypothalamic-pituitary-adrenal axis and antidiuretic hormone production and release, with implications for both acute management and survival. Secondary injuries, occurring hours to weeks after TBI, result in both temporary and permanent alterations in pituitary function. At five years after moderate to severe TBI, nearly 30% of children suffer from hypopituitarism. Growth hormone deficiency and disturbances in puberty are the most common; however, any part of the hypothalamic-pituitary axis can be affected. In addition, endocrine abnormalities can improve or worsen with time, having a significant impact on children’s quality of life both acutely and chronically. Since primary and secondary injuries from TBI commonly result in transient or permanent hypopituitarism, we conclude that survivors should undergo serial screening for possible endocrine disturbances. High indices of suspicion for life threatening endocrine deficiencies should be maintained during acute care. Additionally, survivors of TBI should undergo endocrine surveillance by 6–12 months after injury, and then yearly, to ensure early detection of deficiencies in hormonal production that can substantially influence growth, puberty and quality of life.

Altered stress system reactivity after pediatric injury: Relation with post-traumatic stress symptoms

“…Our findings converge with prior studies emphasizing that neuroendocrine abnormalities are not strongly related to severity of TBI and may emerge during chronic stages of recovery (Reifschneider et al, 2015). There is a paucity of literature on long-term neuroendocrine changes after physical injury in youth.…”

“…Chronic exposure to adversity has the potential to alter the set-point or threshold of HPA activity and reactivity, resulting in either over- or underactivity (Yehuda et al, 2010). Although acute stress reactions may be adaptive, the cumulative effects of chronic activation of these environmentally sensitive systems contribute to poor physical and psychological health, including internalizing disorders (Lupien et al, 2009), immune dysfunction, hypertension, insulin resistance (McEwen, 1998; Pacella et al, 2013), and hypopitutitarism (Reifschneider et al, 2015). …”

“…Alteration in these structures likely contributes to hypopituitarism, growth hormone deficiency and pubertal disturbances that can evolve or persist years after injury and are reported in nearly 30% of children with moderate to severe TBI (Reifschneider et al, 2015). Endocrine dysfunction, particularly precocious puberty and hypothyroidism, has been noted in youth during the first year after mild to moderate TBI (Kaulfers et al, 2010).…”

Social dysfunction after pediatric traumatic brain injury: A translational perspective

“…The narrow pituitary stalk is vulnerable to direct damage by mechanical compression, shearing or vascular injury, or indirectly compromised by brain swelling (Dusick et al, 2012; Reifschneider et al, 2015). Haemorrhage, necrosis and fibrosis of the pituitary stalk, anterior and posterior pituitary have been reported upon autopsy after fatal TBI (Klose and Feldt-Rasmussen, 2015; Kornblum and Fisher, 1969; Tanriverdi and Kelestimur, 2015), and amongst survivors of adult TBI, pituitary atrophy is evident by MRI up to at least 11 months post-injury (Maiya et al, 2008).…”

“…In recent years, numerous studies have identified hypopituitarism as a common consequence of TBI, although the reported incidence varies considerably depending upon assay methodology, diagnostic criteria, patient selection, and duration between injury and evaluation (Reifschneider et al, 2015; Richmond and Rogol, 2014). Growth hormone and gonadotropin deficiencies are the most common pituitary hormone abnormalities reported in TBI patients (Silva et al, 2015), however, any part of the hypothalamic-pituitary axis can be affected.…”